Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. Proteins are tagged for degradation with a small protein called ubiquitin; the tagging reaction is catalyzed by enzymes called ubiquitin ligases. Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin molecules; the result is a polyubiquitin chain, bound by the proteasome, allowing it to degrade the tagged protein. The degradation process yields peptides of about seven to eight amino acids long, which can be further degraded into shorter amino acid sequences and used in synthesizing new proteins. Proteasomes are found inside all eukaryotes and archaea, in some bacteria. In eukaryotes, proteasomes are located both in the cytoplasm.
In structure, the proteasome is a cylindrical complex containing a "core" of four stacked rings forming a central pore. Each ring is composed of seven individual proteins; the inner two rings are made of seven β subunits. These sites are located on the interior surface of the rings, so that the target protein must enter the central pore before it is degraded; the outer two rings each contain seven α subunits whose function is to maintain a "gate" through which proteins enter the barrel. These α subunits are controlled by binding to "cap" structures or regulatory particles that recognize polyubiquitin tags attached to protein substrates and initiate the degradation process; the overall system of ubiquitination and proteasomal degradation is known as the ubiquitin–proteasome system. The proteasomal degradation pathway is essential for many cellular processes, including the cell cycle, the regulation of gene expression, responses to oxidative stress; the importance of proteolytic degradation inside cells and the role of ubiquitin in proteolytic pathways was acknowledged in the award of the 2004 Nobel Prize in Chemistry to Aaron Ciechanover, Avram Hershko and Irwin Rose.
Before the discovery of the ubiquitin–proteasome system, protein degradation in cells was thought to rely on lysosomes, membrane-bound organelles with acidic and protease-filled interiors that can degrade and recycle exogenous proteins and aged or damaged organelles. However, work by Joseph Etlinger and Alfred Goldberg in 1977 on ATP-dependent protein degradation in reticulocytes, which lack lysosomes, suggested the presence of a second intracellular degradation mechanism; this was shown in 1978 to be composed of several distinct protein chains, a novelty among proteases at the time. Work on modification of histones led to the identification of an unexpected covalent modification of the histone protein by a bond between a lysine side chain of the histone and the C-terminal glycine residue of ubiquitin, a protein that had no known function, it was discovered that a identified protein associated with proteolytic degradation, known as ATP-dependent proteolysis factor 1, was the same protein as ubiquitin.
The proteolytic activities of this system were isolated as a multi-protein complex called the multi-catalytic proteinase complex by Sherwin Wilk and Marion Orlowski. The ATP-dependent proteolytic complex, responsible for ubiquitin-dependent protein degradation was discovered and was called the 26S proteasome. Much of the early work leading up to the discovery of the ubiquitin proteasome system occurred in the late 1970s and early 1980s at the Technion in the laboratory of Avram Hershko, where Aaron Ciechanover worked as a graduate student. Hershko's year-long sabbatical in the laboratory of Irwin Rose at the Fox Chase Cancer Center provided key conceptual insights, though Rose downplayed his role in the discovery; the three shared the 2004 Nobel Prize in Chemistry for their work in discovering this system. Although electron microscopy data revealing the stacked-ring structure of the proteasome became available in the mid-1980s, the first structure of the proteasome core particle was not solved by X-ray crystallography until 1994.
In 2018, the first atomic structures of the human 26S proteasome holoenzyme in complex with a polyubiquitylated protein substrate were solved by cryogenic electron microscopy, revealing mechanisms by which the substrate is recognized, deubiquitylated and degraded by the human 26S proteasome. The proteasome subcomponents are referred to by their Svedberg sedimentation coefficient; the proteasome most used in mammals is the cytosolic 26S proteasome, about 2000 kilodaltons in molecular mass containing one 20S protein subunit and two 19S regulatory cap subunits. The core provides an enclosed cavity in which proteins are degraded; each end of the core particle associates with a 19S regulatory subunit that contains multiple ATPase active sites and ubiquitin binding sites. An alternative form of regulatory subunit called the 11S particle can associate with the core in the same manner as the 19S particle; the number and diversity of subunits contained in the 20S core particle depends on the organism.
All 20S particles consist
Seabridge Gold is a Toronto-based North American resource exploration company. It owns Kerr Sulphurets Mitchell, a copper-gold-silver-molybdenum porphyry project in northern British Columbia. KSM's proven-probable reserves amount to 38.8 million ounces of gold, 183 million ounces of silver, 10.2 billion pounds of copper and 207 million pounds of molybdenum. The property is part of a bigger deposit containing another gold project known as Snowfield; the KSM project will cost more than $4.7 billion to build and funding is not yet in place. Gold reserves at the Courageous Lake deposit total 6.5 million ounces. The company was incorporated as Chopper Mines Incorporated on September 14, 1979, it was renamed Dragoon Resources Ltd on November 9, 1984, Seabridge Resources Ltd on May 20, 1998, before adopting its current name on June 20, 2002. In July 2002, Seabridge purchased 100% of its second largest gold property, Courageous Lake in the NWT from Newmont Mining and Total Resources for $5.5 million plus a 2% NSR royalty.
The project at that time reported an historical resource of 5.9 million ounces of gold. The 100% owned Courageous Lake project located in Northwest Territories comprises 59 mining leases totalling more than 67,000 acres covering 85% of Matthews Lake Greenstone Belt and containing one of the largest undeveloped gold deposits in Canada; the 2017 drill program confirmed the presence of a gold-bearing formations. Subsequent work has found the potential for a large porphyry system below the lithocap which will be targeted in 2020 drilling. In conjunction with its exploration program, Seabridge is undertaking environmental work to carry out remediation programs to mitigate impacts of historical mining activity as well as community engagement. In June 2001 Seabridge purchased the Kerr Sulphurets Mitchell property from Placer Dome for 500,000 common shares, 5000 warrants and royalty payments capped at C$4.5 million. The project consisted of two contiguous claim blocks in the Iskut-Stikine region in British Columbia 20 kilometres southeast of the Eskay Creek Mine.
When Seabridge acquired it, the project hosted two distinct deposits which were modelled separately by Placer Dome Limited. At the two deposits, Placer Dome had estimated an historical indicated gold resource of 2.1 million ounces, with an additional 1.3 million ounces of gold in the inferred resource category as well as 2.8 billion pounds of copper resources. KSM's resources stand at 38.8 million ounces of gold, 183 million ounces of silver, 10.2 billion pounds of copper and 207 million pounds of molybdenum. The 100% owned KSM project located in north-western British Columbia has proven and probable reserves of 38.million ounces of gold and 10.2 billion pounds of copper, making it the largest gold reserve in Canada and one of the largest in the world. The project's EA Application received provincial government approval in July, 2014. Final federal approval was received in December, 2014. Seabridge purchased a 100% interest in Snowstorm from PFR Gold Holdings for 700,000 Seabridge common shares and 500,000 common share purchase warrants exercisable for four years.
Additional payments of $2.5 million are due on condition of exploration activities and $5 million upon delineation of additional gold resources. An initial drill program in 2019 has targeted a possible Getchell Trend type of high grade gold deposit
The Myanmar national football team represents Myanmar in international football and is controlled by the Myanmar Football Federation. It was known as the Burma national football team until 1989. During heyday, Burma finished second in the 1968 Asian Cup, participated in the Summer Olympics in 1972 and in the Asian Games and having won the Asian Games twice. No participation in World Cup qualification was made for the rest of 20th century, contributing to the downfall of the national side. Since renamed, Myanmar's highest achievement is the silver medal in 1993. Myanmar played its first World Cup qualifiers in 2007 in the 2010 World Cup qualifiers, losing 0–7 and 0–4 to China. Burma sent players to the Philippines in 1954 Asian Games and captured a bronze medal, behind Taiwan and South Korea. On the other hand, the nation was not expected to contend for a medal in the Olympic-type Asian Games. In the meantime, this delegation became the first male Burmese team to win a continental medal, but this was only the beginning.
Against all odds, the team of Burma bettered their 1954 effort by winning the gold medal in the Asian Games, which were held at Bangkok in the mid-1960s. In that tournament, Burma beat Iran in the gold-medal game; the 1966 Asian Games gold medal winning squad established itself as one of the two best teams in the region as it finished as runner-up to Iran at the 1968 Asian Cup. After claiming silver in 1968, the men's soccer team had a strong performance in the early 1970s as it won the right to compete in the 1972 Summer Olympics, which were held at Munich, upon being one of the three finalists in the Asian tournament. Despite losing all matches, the Burmese players captured the Fair Play Award; the following year, the nation earned its fifth consecutive Southeast Asian Games gold medal at Singapore City. Three years before that, the national team wrote their most important chapter: they captured the continental title for the second time in a row, after the Burmese Olympic Committee sent footballers to Thailand for the 1970 Asian Games.
Burma thus became the second soccer squad to win the Asian tournament twice. They were declared national heroes in Rangoon, the capital of Burma, with their second consecutive gold medal in men's soccer. During this golden era, Burma produced many talented footballers. One among them is Suk Bahadur, now considered as the greatest Burmese footballer of all times for his outstanding contribution to Burmese football. Over the following years, due in large part to several problems in the country, the national side was not able to defend its Asian title. During the era, Burma had been unable to achieve similar results like the golden age, due to many factors; the collapse of whole Burmese football system during the rule of Ne Win and the junta, had a negative effect for Burmese team. Lack of funding, poor infrastructure, affected many Burmese players to seek their opportunity in another nations, or to retire and went disappearance. On the same time, the rise of Malaysia and Vietnam and the Philippines, had made Myanmar's ability faded away.
The series of decline had made Myanmar from a continental power to reduce into one of Asia's weakest teams. Despite this, Myanmar managed to win silver medal in 1993 Southeast Asian Games, after losing to Thailand in the final, or the 2004 Tiger Cup when Myanmar won bronze. Myanmar's 2011 reforms had been a major point of turning Myanmar's football, which had declined since 1970s. During this era, a new wave of Burmese football had arrived with the change of Myanmar's political climate, after many years under junta's rule; the arrival of Gerd Zeise, a German manager, had been the crucial point. Under Gerd, Myanmar's football since reforms has witnessed a significant progress; the U-20 Myanmar team qualified to Myanmar's first FIFA tournament, the 2015 FIFA U-20 World Cup after going to the semi-finals in the 2014 AFC U-19 Championship as host. In 2016 AFF Suzuki Cup, Myanmar, as host, once again went to semi-finals, only losing to eventual champions, Thailand. Between these successes, a lot of problems remain.
Myanmar's football capability has been questioned after their disastrous 2018 World Cup qualification. Once again, Myanmar failed to qualify for 2019 AFC Asian Cup, when they suffered a tremendous 1–5 defeat on the hand of Kyrgyzstan. Under Antoine Hey, Myanmar had an unsuccessful 2018 AFF Championship, with the team was knocked out from the group stage, Hey resigned aftermath; the national team plays most of its home matches in Thuwunna Stadium in Myanmar. The stadium is more up-to-date than Bogyoke Aung San Stadium, it was upgraded to a seating capacity of 50,000 spectators from capacity of 32000 in 2013. The Myanmar national team team used to play with a kit made by FBT; this contract lasted until 2018. In November 2018, the Myanmar national team signed a six-year contract with Warrix Sports; the sports kit sponsorship contract is valued at US$5.67 million and it will run from 1 November 2018 to 31 December 2024. On 6 November 2018, Warrix introduced a new Myanmar home and away kit. Myanmar's home kits is a red shirt with red shorts and red socks while the away kits is a white shirt with white shorts and white socks.
The kits were made by Adidas. Disqualified in 2006 for withdrawing from qualification in 2002. Initial
London Britannia Airport was a proposed six-runway airport to be built on an artificial island in the River Thames estuary to serve London, comparable to a similar approach taken with Hong Kong International Airport. The proposal, dubbed "Boris island" by the media, reflecting the support for the project from former London Mayor Boris Johnson; the scheme was proposed by Testrad an agency formed by Johnson but now involving other partners, was rejected by the airport commission in January 2014. Plans for a Thames Estuary Airport go back many years; the idea was revived in 2008 by the Mayor of London, Boris Johnson, to be located towards the Shivering Sands area, north-east of Whitstable. The deputy mayor, Kit Malthouse, had supported a Thames estuary airport since before taking office. In November 2008, the mayor appointed Doug Oakervee to lead the Greater London Authority's preliminary feasibility study, which determined in October 2009 that there is "no logical constraint" to the plan; the name London Britannia Airport was adopted for the latest iteration of the idea presented in November 2013.
This proposal would mean the closure of Heathrow Airport. In early 2014 it was revealed that the Airports Commission, in its interim report, did not recommend the London Britannia proposal for further analysis. Proponents argue the scheme's big advantage is that it would avoid flying over densely populated areas and the noise pollution and other problems that causes; some local councils and the Royal Society for the Protection of Birds oppose the plan, as do current London airports. Critics suggest the scheme is too expensive. "London Britannia Airport Plans: In Pictures". Londonist. 12 November 2013. Archived from the original on 11 February 2020. Retrieved 11 February 2020. "Europe's Hub Airport: Connects City Regions and London to the World". TESTRAD/Gensler. November 2013. Archived from the original on 11 February 2020. Retrieved 11 February 2020
Sarenga is a village, with a police station, in Sarenga CD Block in Khatra subdivision of Bankura district in the state of West Bengal, India. As per 2011 Census of India Sarenga had a total population of 5,888 of which 2,996 were males and 2,892 were females. Population below 6 years was 592; the total number of literates in Sarenga was 4,486. Sarenga police station has jurisdiction over Sarenga CD Block; the area covered is 235.68 km2with a population of 95,096. The headquarters of Sarenga CD Block are located at Sarenga. State Highway 9, running from Durgapur to Nayagram, pass through Sarenga. Sarenga Block Public Health Centre functions as the central facility in Sarenga CD Block, with a Public Health Centre at Krishnapur and 17 subcentres
Finish is the brand name of a range of dishwasher detergent products sold by the consumer products manufacturer Reckitt Benckiser. The tablets of the original product are surfactants which cleans water hardness and break down foods containing bleaches and proteins to remove bleachable stains and produce enzymes and foams, it is specially designed for dishwashers. The brand is marketed under the name "Calgonit" in North America. In the early 1950s, the increased use of molded plastic dinnerware posed a number of problems; the Finish brand was created in 1953 by the US company Economics Laboratory. Taking advantage of research into the needs of the dairy and food industry, Eco-Lab launched two new products in the household dishwashing machine — Electrasol and Finish, a new premium product in 1953. In 1969, they introduced the first biologically dusty product. J. A. Benckiser acquired the Consumer Products division of Eco-lab Inc. in 1987. In 1995, the first two-ply powder tablet was introduced, in 1999 the red Powerball capsule, in 2008, the Finish Quantum and the first three-chamber molded capsule.